Studies were directed toward defining the role of disorders of lymphocyte maturation and of immunoregulatory cell interactions in the pathogenesis of immune dysfunctions. Recombinant DNA technology has been applied to the study of the arrangement and rearrangement of immunoglobulin genes in lymphocytic leukemias. A hierarchy of gene rearrangements was suggested with a rearrangement of immunoglobulin heavy chain genes preceeding light chain genes and kappa gene rearrangements or deletions preceeding lambda. All hairy cell leukemic cells studied and lymphoid blast crisis cells from patients with chronic myelogeneous leukemia were shown to be B cell presursors on the basis of their immunoglobulin gene rearrangements. Furthermore, non-T non-B cell leukemic cells that did not react with anti-T-cell monoclonal antibodies represented B cell precursor leukemias. Using a monoclonal antibody, anti-Tac, the human receptor for T cell growth factor (TCGF, interleukin-2) has been purified to homogeneity. The receptor is a 55,000 dalton glycoprotein composed of a 33,000 dalton peptide backbone tht is post translationally modified by introduction of N and O linked carbohydrate as well as sialic acid yielding mature receptors. The anti-Tac monoclonal inhibits (1) in vitro T cell proliferation induced by antigens, the development of cytotoxic T cells and T cell dependent B cell immunoglobulin production. Leukemias of helper T cells (Sezary leukemia cells) are Tac antigen negative. In contrast the adult T cell leukemia which is associated with the type C retrovirus (human T cell leukemia/lymphoma virus, HTLV) universally displays large numbers of TCGF receptors on the cell surface. The consistant display of TCGF receptors which may be aberrant in size on adult T cell leukemia cells may play a role in the uncontrolled growth of these cells.